Total Synthesis of Altissimacoumarin D, a Small Molecule Sirtuin1 Activator

The total synthesis of the plant natural product altissimacoumarin D was achieved by the Mitsunobu alkylation of isofraxidin by geraniol. Isofraxidin was prepared from 2,4-dihydroxybenzaldehyde in five steps. The key reaction was the Knoevenagel condensation of an ortho-hydroxybenzaldehyde with Meldrum’s acid under neutral conditions in water and one-pot acid catalyzed cyclization to the coumarin

Development of a Mesoscale Finite Element Constitutive Model for Fiber Kinking

A mesoscale finite element material model is proposed to analyze structures that fail by the fiber kinking damage mode. To evaluate the assumptions of the mesoscale model, the results were compared with those of a high-fidelity micromechanical model. A direct comparison between the two models shows remarkable correlation, indicating that the key features of the fiber kinking phenomenon are appropriately accounted for in the mesoscale model. The mesoscale model is applied to structural analysis cases to demonstrate the capabilities of the model. A verification study is conducted with an unnotched compression specimen and preliminary validation is demonstrated with a notched compression specimen. The results show that the model is successful at representing the kinematics of fiber kinking while at the same time highlighting the need for further verification and validation

Modeling Fiber Kinking at the Microscale and Mesoscale

A computational micromechanics (CMM) model is employed to interrogate the assumptions of a recently developed mesoscale continuum damage mechanics (CDM) model for fiber kinking. The CMM model considers an individually discretized three dimensional fiber and surrounding matrix accounting for nonlinearity in the fiber, matrix plasticity, fiber/matrix interface debonding, and geometric nonlinearity. Key parameters of the CMM model were measured through experiments. In particular, a novel experimental technique to characterize the in situ longitudinal compressive strength of carbon fibers through indentation of micropillars is presented. The CDM model is formulated on the basis of Budiansky's fiber kinking theory (FKT) with a constitutive deformation-decomposition approach to alleviate mesh size sensitivity. In contrast to conventional mesoscale CDM models that prescribe a constitutive response directly, the response of the proposed model is an outcome of material nonlinearity and large rotations of the fiber direction following FKT. Comparison of the predictions from the CMM and CDM models shows remarkable correlation in strength, post-peak residual stress, and fiber rotation, with less than 10% difference between the two models in most cases. Additional comparisons are made with several fiber kinking models proposed in the literature to highlight the efficacy of the two models. Finally, the CMM model is exercised in parametric studies to explore opportunities to improve the longitudinal compression strength of a ply through the use of nonconventional microstructures

Transverse cracking of cross-ply laminates: A computational micromechanics perspective

Transverse cracking in cross-ply carbon/epoxy and glass/epoxy laminates in tension is analyzed by means of computational micromechanics. Longitudinal plies were modeled as homogenized, anisotropic elastic solids while the actual fiber distribution was included in the transverse plies. The mechanical response was obtained by the finite element analysis of a long representative volume element of the laminate. Damage in the transverse plies was triggered by interface decohesion and matrix cracking. The simulation strategy was applied to study the influence of ply thickness on the critical stress for the cracking of the transverse plies and on the evolution of crack density in 02=90n=2 s laminates, with n = 1, 2, 4 and 8. It was found that the transverse ply strength corresponding to the initiation and propagation of a through-thickness crack was independent of the ply thickness and that the transverse strength of carbon/epoxy laminates was 35% higher than that of the glass fiber counterparts. In addition, the mechanisms of crack initiation and propagation through the thickness as well as of multiple matrix cracking were ascertained and the stiffness reduction in the 90 ply as a function of crack density was computed as a function of the ply thickness.The authors kindly acknowledge the support of the Spanish Ministry of Economy and Competitiveness through the project MAT2012-37552. CSL acknowledges the support of the Spanish Ministry of Economy and Competitiveness through the Ramon y Cajal program

Multiscale modelling of thermoplastic woven fabric composites: From micromechanics to mesomechanics

The mechanical properties of woven composites can be predicted by using a multiscale modelling approach. The starting point to its application is the microscale (the level of fibres, matrix and interfaces), that allows the computation of the homogenised behaviour of the yarn. The aim of this work was to predict the yarn-level behaviour of a thermoplastic-based woven composite in order to allow the formulation of a representative constitutive model that can be used to predict ply properties at the mesoscale. To accomplish this purpose, an in situ characterisation of the microconstituents was carried out. This served to generate inputs for three different representative volume element (RVE) models that allowed predicting the yarn longitudinal, transverse and shear responses. These mechanical characteristics allowed the determination of homogenised yarn constitutive behaviour which was found to be characterised by significant non-linearity until failure, specially in transverse and shear directions.The research leading to the developments described received funding of the project ADVANSEAT; a collaborative R&D project led by Grupo Antolín, and partially supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO). C.S. Lopes also acknowledges the support of MINECO through the Ramón y Cajal fellowship (RYC-2013-14271)

Resistance Curves in the Tensile and Compressive Longitudinal Failure of Composites

This paper presents a new methodology to measure the crack resistance curves associated with fiber-dominated failure modes in polymer-matrix composites. These crack resistance curves not only characterize the fracture toughness of the material, but are also the basis for the identification of the parameters of the softening laws used in the analytical and numerical simulation of fracture in composite materials. The method proposed is based on the identification of the crack tip location by the use of Digital Image Correlation and the calculation of the J-integral directly from the test data using a simple expression derived for cross-ply composite laminates. It is shown that the results obtained using the proposed methodology yield crack resistance curves similar to those obtained using FEM-based methods in compact tension carbon-epoxy specimens. However, it is also shown that the Digital Image Correlation based technique can be used to extract crack resistance curves in compact compression tests for which FEM-based techniques are inadequate

Synthesis of natural ether lipids and 1-O-hexadecylglycero-arylboronates via an epoxide-ring opening approach: Potential antifouling additives to marine paint coatings

In this paper a new and efficient procedure for the synthesis of natural 1-O- alkyl glyceryl ethers such as chimyl (1), batyl (2) and selachyl (3) is described. Alkyl glycidyl ethers (4-6) were synthetized using solvents free reactions. A stereospecific ring-opening reaction of epoxides (4-6) with phenylboronic acid in dry dioxane, giving rise to cyclic arylboronates in high yields (90-98%). Seven new 1-O-hexadecylglycero-arylboronates (7-f) and chimyl alcohol (1) were evaluated in laboratory antifouling assays

Guidelines for the recording and evaluation of pharmaco-EEG data in man: the International Pharmaco-EEG Society (IPEG)

The International Pharmaco-EEG Society (IPEG) presents updated guidelines summarising the requirements for the recording and computerised evaluation of pharmaco-EEG data in man. Since the publication of the first pharmaco-EEG guidelines in 1982, technical and data processing methods have advanced steadily, thus enhancing data quality and expanding the palette of tools available to investigate the action of drugs on the central nervous system (CNS), determine the pharmacokinetic and pharmacodynamic properties of novel therapeutics and evaluate the CNS penetration or toxicity of compounds. However, a review of the literature reveals inconsistent operating procedures from one study to another. While this fact does not invalidate results per se, the lack of standardisation constitutes a regrettable shortcoming, especially in the context of drug development programmes. Moreover, this shortcoming hampers reliable comparisons between outcomes of studies from different laboratories and hence also prevents pooling of data which is a requirement for sufficiently powering the validation of novel analytical algorithms and EEG-based biomarkers. The present updated guidelines reflect the consensus of a global panel of EEG experts and are intended to assist investigators using pharmaco-EEG in clinical research, by providing clear and concise recommendations and thereby enabling standardisation of methodology and facilitating comparability of data across laboratories

Fucosylated Chondroitin Sulfate Inhibits Plasmodium Falciparum Cytoadhesion And Merozoite Invasion.

Sequestration of Plasmodium falciparum-infected erythrocytes (Pf-iEs) in the microvasculature of vital organs plays a key role in the pathogenesis of life-threatening malaria complications, such as cerebral malaria and malaria in pregnancy. This phenomenon is marked by the cytoadhesion of Pf-iEs to host receptors on the surfaces of endothelial cells, on noninfected erythrocytes, and in the placental trophoblast; therefore, these sites are potential targets for antiadhesion therapies. In this context, glycosaminoglycans (GAGs), including heparin, have shown the ability to inhibit Pf-iE cytoadherence and growth. Nevertheless, the use of heparin was discontinued due to serious side effects, such as bleeding. Other GAG-based therapies were hampered due to the potential risk of contamination with prions and viruses, as some GAGs are isolated from mammals. In this context, we investigated the effects and mechanism of action of fucosylated chondroitin sulfate (FucCS), a unique and highly sulfated GAG isolated from the sea cucumber, with respect to P. falciparum cytoadhesion and development. FucCS was effective in inhibiting the cytoadherence of Pf-iEs to human lung endothelial cells and placenta cryosections under static and flow conditions. Removal of the sulfated fucose branches of the FucCS structure virtually abolished the inhibitory effects of FucCS. Importantly, FucCS rapidly disrupted rosettes at high levels, and it was also able to block parasite development by interfering with merozoite invasion. Collectively, these findings highlight the potential of FucCS as a candidate for adjunct therapy against severe malaria.581862-7